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Surgical closure of a patent ductus arteriosus was performed in 8 low birthweight infants suffering from cardiorespiratory failure secondary to a large left-to-right shunt. Mortality from the operation was nil, but only 4 (50%) ultimately survived. Earlier intervention may reduce mortality in these high-risk infants.
17 very low birthweight infants (mean birthweight 850 g) with large patent ductus arteriosus (PDA) were studied by echocardiography before and after treatment with indomethacin. Before treatment left heart dimensions were increased suggesting large left-to-right shunt. Echographic measurements of augmented left ventricular (LV) contraction could be attributed to increase in preload, and reduction in afterload in PDA. After indomethacin, in infants showing clinical response, left heart dimensions returned rapidly to normal and LV contraction became normal or reduced. Two infants had reduced LV contraction with persistent pulmonary oedema suggesting LV failure. In contrast, infants showing no clinical response to the drug also had no significant changes in echographic measurements. Right ventricular systolic time intervals (RPEP/RVET) did not alter after indomethacin treatment in either group, suggesting that the drug does not increase pulmonary vascular resistance.
Thirty very low birthweight (VLBW) infants (mean gestational age 28.9 weeks; mean birthweight 1138 g) with symptomatic patent ductus arteriosus (PDA) were entered in a randomised double blind trial of indomethacin treatment. The mean age at diagnosis was 7.6 days and at entry to the trial 10.7 days. Before treatment for PDA the indomethacin and placebo groups were well matched for gestational age, birthweight, incidence of respiratory distress requiring mechanical ventilation, and fluid intake. Treatment was up to three daily doses of indomethacin 0.2 mg/kg or placebo by gastric tube and fluid restriction. During treatment there was a response in 13 out of 15 in the indomethacin group and in 3 out of 15 in the control group (P less than 0.001), but because of relapse the effect was maintained in only 7 out of 15 and 2 out of 15 respectively (P less than 0.05). No abnormalities were attributable to indomethacin, which is a safe and effective treatment for PDA in the VLBW infant, but the high relapse rate despite fluid restriction suggests that the best treatment has still to be found.
Pulse wave patterns were analysed in 10 term and 10 preterm infants with patent ductus arteriosus (PDA) and in 2 matched control groups. A non-invasive technique was used to record the pulse waves from the axillary artery. The pulsatile ratio was calculated as the quotient between the amplitude of the incisural notch and the peak of the pulse wave above the end diastolic baseline. The pulsatile ratio was considerably lower in preterm and term infants with PDA compared with the ratio after closure of the ductus and the ratio in control infants. A pulsatile ratio less than 0.50 indicates the presence of a large PDA whereas a ratio over 0.55 is normal. The technique may be used to document and evaluate arterial pulse wave patterns and may be a useful diagnostic tool.
Intravenous indomethacin was given to 36 neonates with a patent ductus arteriosus who where receiving ventilatory support for respiratory distress syndrome. Permanent closure of the ductus arteriosus occurred in 21 (58%) infants and in this group the mean 24 hour plasma indomethacin concentration was 0.37 micrograms/ml. Partial success was achieved in 6 (17%) infants (mean 24 hour indomethacin concentration 0.34 micrograms/ml) but in 9 patients (mean 24 hour indomethacin concentration 0.29 micrograms/ml) there was no clinical change. Although the mean 24 hour indomethacin concentration was lower in the group with no clinical change, this was not statistically significant. Five of the 21 patients in whom there was permanent closure of the ductus required more than one dose of indomethacin. The possible effects of birthweight and age at indomethacin treatment were difficult to separate because of the high negative correlation between these two variables. The chance of closure was enhanced significantly if the patient had either a birthweight of at least 1 kg or the age at indomethacin treatment did not exceed 10 days, or both. Six hour but not 24 hour indomethacin concentrations were higher in patients with a high birthweight treated at an early age.
The effect of indomethacin treatment of patent ductus arteriosus (PDA) on blood pressure was studied in 24 preterm infants. PDA was diagnosed clinically and confirmed by echocardiography; the effect of treatment was monitored echocardiographically. Hourly intra-arterial recordings of systolic, diastolic, and mean blood pressure were averaged for the 48 hours before the first dose of indomethacin and for each of the three 24 hour periods after the first dose. In the 16 infants in whom treatment was successful, the average mean blood pressure increased significantly over the three days after the first dose. On the third day after beginning treatment with indomethacin the average increase in mean blood pressure was 10.4 mm Hg. Fourteen of 16 infants showed an increase of 4 mm Hg or more. Systolic and diastolic blood pressure increased significantly by similar amounts, so the pulse pressure did not change. In the eight infants treated unsuccessfully, there was no consistent change in any of the blood pressure parameters. The maximum increase in mean blood pressure was 3 mm Hg. These findings confirm that PDA is one of the determinants of blood pressure in preterm infants. The effect is general and there is no consistent change in pulse pressure when a PDA is closed. A general increase in blood pressure is a useful additional indicator of successful medical ductal closure.
The aim of this study was to re-examine the accuracy of the left atrial aortic root ratio (LA:Ao) as a marker of significant patent ductus arteriosus (PDA) in the preterm infant by comparison with direct Doppler echocardiographic assessment. Fifty six infants (< 1500 g) had 463 serial echocardiograms. Firstly the LA:Ao was measured, then the duct was imaged and classified as wide open, restricting, or closed according to two dimensional and Doppler criteria. Probability analysis was performed to test the ability of the LA:Ao to discriminate between a wide open PDA and a restricting or closed duct. Mean LA:Ao was 1.17 and 1.21 when the duct was respectively closed or restricting compared with 1.61 when wide open. Using a LA:Ao of 1.5 as a cut off gives a sensitivity of 79% and specificity of 95% and increases the accuracy over the recommended levels of 1.3 and 1.4. With this cut off there were 20/94 false negatives, these were associated with scans on day 1 and large interatrial shunts. The sensitivity of the LA:Ao increased to 88% if only scans performed after day 1 were analysed. For diagnosing a PDA after day 1, the positive likelihood ratio of an LA:Ao of 1.5 or more was 17.5, and the negative likelihood ratio of an LA:Ao < 1.5 was 0.13. The LA:Ao is still a useful tool in the diagnosis of PDA. It is a simple method which needs less skill and resources than direct PDA imaging and is feasible on neonatal units without direct access to echocardiographic expertise. Its use on the first postnatal day is not recommended.
The left ventricular Frank-Starling response was studied in 15 preterm infants, less than 1500 g birth weight, and in 16 fullterm infants with patent ductus arteriosus. Left ventricular end diastolic volume (LVEDV), stroke volume, and cardiac output were calculated from biplane echocardiographic images with a modified Simpson's rule, and the left ventricular function curve was obtained by standardising with birth weight and body length. In the relationship between LVEDV and stroke volume, the slope of the regression line was significantly milder in preterm than in fullterm infants; however, there was no significant difference in the relationship between LVEDV and cardiac output. The heart rate was significantly higher in preterm than in fullterm infants. Our data indicated that the premature infants had less left ventricular reserve capacity to respond to the increased preload through the left-to-right ductal shunting than the mature ones, and that the high pulse rate made it possible to generate adequate cardiac output in premature infants.
AIM: To evaluate the efficiency and side effects of ibuprofen for the early treatment of patent ductus arteriosus (PDA) and compare it with indomethacin. METHODS: Forty preterm infants with gestational ages of less than 33 weeks, with respiratory distress syndrome (RDS) and echocardiographically confirmed PDA, were randomly assigned at days 2 to 3 of life to receive either intravenous indomethacin 3 x 0.2 mg/kg at 12 hour intervals or intravenous ibuprofen 1 x 10 mg/kg, followed by 5 mg/kg 24 and 48 hours later. RESULTS: PDA closed in 15 of 20 patients from the indomethacin group (75%) and in 16 of 20 (80%) from the ibuprofen group. Seven patients (three indomethacin, four ibuprofen) required a second treatment with indomethacin and in five (three in the indomethacin group and two in the ibuprofen group) the duct was ultimately ligated. Ibuprofen patients had a better urinary output and showed no increase in serum creatinine concentrations compared with the indomethacin group. Ibuprofen was not associated with any other side effect. CONCLUSIONS: Ibuprofen treatment seems to be as efficient as indomethacin in closing PDA on the third day of life in preterm infants with respiratory distress syndrome and seems to have fewer renal side effects.
AIMS: To identify the patent ductus arteriosus (PDA) shunt flow pattern using Doppler echocardiography; and to assess whether it could be used to predict the development of clinically significant PDA. METHODS: Premature infants weighing under 1500 g, who required mechanical ventilation, and in whom daily echocardiography could be performed from day 1 until the ductus closed, and on day 7 to confirm closure, were studied. The PDA shunt flow was identified from four Doppler patterns, and the closed pattern of a closed duct was also presented. Clinically significant PDA was diagnosed when there was colour Doppler echocardiographic evidence of left to right ductal shunt associated with at least two of the following clinical signs: heart murmur (systolic or continuous); persistent tachycardia (heart rate > 160/min); hyperactive precordial pulsation; bounding pulses; and radiographic evidence of cardiomegaly or pulmonary congestion. RESULTS: Of 68 infants enrolled into this study, clinically significant PDA developed in 31. The most recordable sequence of transition change of shunt flow pattern for clinically significant PDA was: pulmonary hypertension pattern, to growing pattern, to pulsatile pattern, to closing pattern, to closed pattern. And that for non-clinically significant PDA was: pulmonary hypertension pattern, to closing pattern, to closed pattern. The growing and the pulsatile patterns were mostly documented in infants with clinically significant PDA. The first documented growing pattern to predict clinically significant PDA gave a sensitivity of 64.5% and a specificity of 81.1%; the first documented pulsatile pattern gave a sensitivity of 93.5% and a specificity of 100%. CONCLUSION: Doppler echocardiographic assessment of PDA shunt flow pattern during the first 4 days of life is useful for predicting the development of clinically significant PDA in premature infants. At that stage, the closing or closed Doppler pattern indicates that infants are not at risk of developing clinically significant PDA; the growing or pulsatile Doppler pattern indicates a continuing risk of developing clinically significant PDA.
AIM: To compare the efficacy and safety of an indomethacin treatment strategy based on serial echocardiographic measurement of patent ductus arteriosus (PDA) flow pattern with a standard protocol. METHODS: Neonates weighing less than 1500 g at birth, who required respiratory support, and who had developed symptomatic PDA, were studied. PDA was confirmed in all infants using colour Doppler echocardiography, and serial observations of the ductal flow pattern were made. Infants randomly assigned to receive conventional indomethacin treatment (protocol group) were given an initial dose of 0.2 mg/kg, followed by 0.1 or 0.2 mg/kg, depending on age, 12 hourly for two further doses, and were eligible for a second course. Those randomly assigned to the ductal flow pattern assessment (ECHO group) received further doses of indomethacin after 24 hours, only if their flow pattern was "pulsatile" or "growing." RESULTS: There was no significant difference in the primary outcome measures between the two groups. The closure rate was 89.1% and 87.2%, respectively, in the protocol and ECHO groups. The mean (SD) doses of indomethacin were significantly higher in the protocol group: 3.2 (1.4) doses compared with 1.6 (0.9) doses. There was a significantly higher incidence of hypoglycaemia, impaired urine output, and gastrointestinal bleeding in the protocol group. CONCLUSIONS: An indomethacin treatment strategy for PDA based on measurement of the ductal flow pattern is associated with a reduction in the total doses of indomethacin administered, and a reduced rate of complications, compared with a conventional protocol. There is no difference in closure rate.
OBJECTIVE: To evaluate the in vivo biocompatibility of three different devices following interventional closure of a patent ductus arteriosus (PDA) in an animal model. MATERIALS AND METHODS: A medical grade stainless steel coil (n = 8), a nickel/titanium coil (n = 10), and a polyvinylalcohol foam plug knitted on a titanium wire frame (n = 11) were used for interventional closure of PDA in a neonatal lamb model. The PDA had been maintained by repetitive angioplasty. Between one and 278 days after implantation the animals were killed and the ductal block removed. In addition to standard histology and scanning electron microscopy, immunohistochemical staining for biocompatibility screening was also undertaken. RESULTS: Electron microscopy revealed the growth of a cellular layer in a cobblestone pattern on the implant surfaces with blood contact, which was completed as early as five weeks after implantation of all devices. Immunohistochemical staining of these superficial cells showed an endothelial cell phenotype. After initial thrombus formation causing occlusion of the PDA after implantation there was ingrowth of fibromuscular cells resembling smooth muscle cells. Transformation of thrombotic material was completed within six weeks in the polyvinylalcohol plug and around the nickel/titanium coil, and within six months after implantation of the stainless steel coil. An implant related foreign body reaction was seen in only one of the stainless steel coil specimens and in two of the nickel/titanium coil specimens. CONCLUSION: After implantation, organisation of thrombotic material with ingrowth of fibromuscular cells was demonstrated in a material dependent time pattern. The time it took for endothelium to cover the implants was independent of the type of implant. Little or no inflammatory reaction of the surrounding tissue was seen nine months after implantation.
BACKGROUND: Surgical closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension in adults carries higher risk than in children. OBJECTIVES: To investigate the application of self-expandable occluders for transcatheter closure of PDA associated with severe pulmonary arterial hypertension in adults, and the assessment of immediate and short-term results. METHODS: 29 adult patients (6 men, 23 women) underwent attempted transcatheter closure of PDA at a mean (standard deviation (SD)) age of 31.1 (11.4) years (range 18-58 years) and a mean (SD) weight of 54.1 (7.1) kg (range 42-71 kg). On the basis of haemodynamic and clinical data obtained before and after trial occlusion, the final duct occlusion was determined and carried out. Radiographs of the chest, electrocardiograms and echocardiograms were used for follow-up evaluation of the treatment within 1 day, 1 month and 3-6 months after successful closure. RESULTS: 20 of the 29 patients had successful occlusion (group 1), and 9 patients failed (named group 2). In group 1, in which occlusion was successful, mean (SD) pulmonary arterial pressures decreased markedly after trial occlusion: 78 (19.3) mm Hg (range 50-125 mm Hg) before occlusion and 41 (13.8) mm Hg (range 23-77 mm Hg) after occlusion. Systemic arterial oxygen saturation was found to be >90% in 19 patients and <90% in the remaining patient before inhalation of oxygen, and >95% during inhalation of oxygen or after occlusion in all 20 patients. In group 2, the occlusion was not successful, because in two patients the device was not available; another two patients showed worsening of symptoms. The other five patients showed increased pulmonary arterial pressures after trial closure; their mean (SD) pulmonary arterial pressures increased by 10.3 (6) mm Hg (4-16 mm Hg) after trial occlusion, and systemic arterial oxygen saturation was 85.5% (2.6%) (range 82.6-88%) before inhalation of oxygen and 94.7% (1.7%) (range 90.7-99.1%) during inhalation of oxygen. In group 1, the dimensions of the left atrium, left ventricle and pulmonary artery increased considerably in 3-6-months of follow-up compared with those of preocclusion. CONCLUSIONS: Transcatheter closure is an effective treatment for adults with PDA associated with reversible severe pulmonary arterial hypertension. Further research is needed for the evaluation of long-term results.
Fatal haemopericardium in a 27 year old pregnant woman was caused by rupture of a dissecting aneurysm of the pulmonary artery. She had an uncorrected patent ductus arteriosus and severe pulmonary hypertension. The wall of the pulmonary artery showed atherosclerosis and cystic medionecrosis.
OBJECTIVES: To determine the benefits of using a single venous catheter and a single angiogram during catheter occlusion of a patient arterial duct with the Rashkind double umbrella compared with those of venous and arterial catheters and multiple angiograms. DESIGN: Retrospective review of case notes. PATIENTS: 103 consecutive patients. The long sheath could not be advanced adequately in two patients. 101 patients had 104 implantations. Median (range) age was 35 (7-549) months and median (range) weight 13 (7-62) kg. Fifty four implantations were performed using the venous and arterial method and 50 using the venous only method. RESULTS: Median procedure times (70 v 90 min), number of angiograms (one v four), and angiographic dye volume used (2 v 7 ml/kg) were significantly reduced using the venous only method compared with those of the venous and arterial method. There was no significant difference in fluoroscopy time (venous only 9 v venous and arterial 10 min). CONCLUSIONS: Considerable improvements can be made in the technique of catheter closure of patent arterial ducts using the Rashkind double umbrella without compromising outcome using venous cannulation alone and a single angiogram, rather than venous and arterial cannulation and multiple angiograms. reduced risk to arteries from cannulation, The benefits are reduced radiation exposure, reduced risk to arteries from cannulation, shorter procedures, and lower equipment costs.
OBJECTIVE: To assess the immediate and mid-term results of transcatheter closure of patent ductus arteriosus (PDA) > or = 4 mm with multiple Gianturco coils. (Transcatheter closure of large PDAs using the Rashkind occluder or the buttoned device is associated with a 7-38% incidence of residual shunt.) METHODS: 19 patients (7 male, 12 female) underwent an attempt at anterograde transcatheter closure with multiple Gianturco coils of a large PDA at a median age of 3.8 yr (range 2 weeks-34 yr) and median weight of 14 kg (range 2.3-80 kg). RESULTS: The median PDA diameter at the narrowest segment was 4.3 mm (range 4-7 mm) and the mean (SD) Qp/Qs was 1.9 (0.8). Each patient had left atrial and left ventricular volume overload. A 4F catheter was used to deliver the coils in all patients. There was immediate and complete closure in 16/18; one patient had residual shunt that was closed at a second procedure and the other had spontaneous disappearance of the residual shunt at the six week visit. A short ductus (angiographic type B) in one patient could not be closed. The median number of coils placed at the first attempt to close the ductus was 4 (range 2-6 coils) and the median fluoroscopy time was 40 minutes (range 13-152 minutes). Mild left pulmonary artery stenosis occurred in the two smallest patients. Coil migration to the lung occurred in 3 patients with retrieval of coils in two patients. All procedures but one were done on an outpatient basis. At a median follow up of 1.6 yr (range 2 weeks-2.2 yr) all patients had complete closure with no new complications. CONCLUSIONS: Anterograde transcatheter closure with multiple Gianturco coils is an effective treatment for most patients with large PDA of diameters up to 7 mm. This technique can be performed in small infants on an outpatient basis without the need for general endotracheal anaesthesia.
The genome is one of the primordial elements of the human being and is responsible for human identity and its transmission to descendants. The gene as such ought not be appropriated or owned by man. However, any sufficiently complete description of a gene should be capable of being protected as intellectual property. Furthermore, all utilisations of a gene or its elements that permit development of processes or new products should be patentable. Ethics, in the sense of moral action, should come into play from the very first stages of research into the human genome. Protection of intellectual and industrial property is of purely legal concern and need not provoke ethical consideration. By contrast, the use of the results of, and in particular the commercialisation of products deriving from, research into the human genome, ought to be subjected to ethical consideration and control. Considering the economic and societal stakes of such research, ethical analysis ought to be at an international level if mistakes and unforeseen risks of conflict are to be avoided.
A large family is described in which patent ductus arteriosus in association with an unusual facial appearance affected nine family members in three generations. The segregation pattern suggests autosomal dominant inheritance with incomplete penetrance with respect to the PDA. The facial features included a broad, high forehead, flat profile, and short nose with a broad, flattened tip.